This proposal employs a rabbit model to study the alterations in autonomic responsiveness exhibited by atopic humans. Sensitization of the rabbits to antigen involves a biweekly immunization schedule begun in the neonatal period, which induces longterm IgE synthesis. Pilot studies demonstrated that cholinergic responsiveness is increased, alpha-adrenergic responsiveness is unchanged and beta-adrenergic responsiveness is reduced in sensitized vs. control rabbits, a pattern which simulates that of atopic nonasthmatic humans. The goals of the proposed studies include establishing the mechanisms by which autonomic responsiveness is altered in the sensitized rabbits, determining which cells and tissues exhibit the alterations, and elucidating the nature of the relationship between immunological stimulation and the development of alterations in autonomic responsiveness. Initial assessment of autonomic alterations relies on in vivo monitoring of any changes in lung mechanics, ventilatory function, pupil size and pulse pressure in response to cholinergic and adrenergic stimuli. In vitro techniques will then be used to initiate studies of the mechanisms involved and to more fully characterize tissue distribution of the alterations. Responses of isolated smooth muscle to cholinergic and adrenergic agents will be correlated with cyclic AMP levels and with specific cell surface receptor numbers and affinities, using direct ligand binding techniques. The relationship between IgE and the development of autonomic alterations is also amenable to examination in this model, since it is a model in which sensitization is experimentally induced and can thus be varied as needed to determine the effects of age (at initiation of sensitization), immunoglobulin classes produced in response to antigen, and active vs. passive sensitization protocols. Finally, a study will be performed to determine if repeated aerosol antigen challenge leads to a pattern of autonomic reactivity typical of asthma in humans.